PROJECT SUMMARY Although there has been an overall decline in HIV incidence in the United States in recent years, new HIV infections have been increasing among populations of men who have sex with men (MSM). Within this context, HIV pre-exposure prophylaxis (PrEP) holds considerable promise as a highly effective biomedical HIV prevention strategy. The effectiveness of PrEP, however, is dependent on treatment adherence, retention in care, and the continued use of condoms. Identifying and addressing factors that detract from these PrEP- relevant behaviors is therefore imperative for maximizing the HIV preventive benefits of PrEP. Hazardous alcohol consumption, and concurrent conditions such as substance use and depression, have been shown to adversely impact a variety of health behaviors, and although these concerns are prevalent among PrEP- prescribed MSM, little work has been conducted to investigate their role in PrEP treatment. The present study involves a two-phased approach designed to 1) gain a better understanding of the associations among alcohol use, concurrent substance use and depression, and PrEP-related behaviors among PrEP-prescribed MSM (UH2 phase); and 2) explore whether addressing hazardous drinking and concurrent conditions can potentially lead to improvements in MSM's PrEP-related behaviors (UH3 phase). The first phase of this research (UH2) will involve 1) up to five focus groups with PrEP-prescribed MSM to explore barriers to PrEP adherence, retention in PrEP-related care, and condom use; with an emphasis on alcohol consumption and concurrent conditions; 2) surveys with 120 PrEP-prescribed MSM to identify rates of, and associations among, PrEP adherence, condomless sex, hazardous drinking, and concurrent conditions; and 3) chart reviews of over 400 PrEP-prescribed MSM to ascertain clinically-identified rates of, and associations among, PrEP adherence, retention in PrEP-related care, sexually transmitted infections, hazardous drinking, and concurrent conditions. Building on this initial work, the second phase of this research (UH3) will entail a pilot randomized controlled trial in which 120 hazardous drinking, PrEP-prescribed MSM will be randomly assigned to receive either a tablet-based, alcohol-reduction brief intervention or treatment-as-usual. Participants assigned to the former condition for whom substance use- and/or depression-related concerns are identified will be provided with links to relevant resources. All trial participants will complete biomarker testing and self-report assessments at baseline, 3-months, and 6-months to assess the preliminary impact of the intervention on alcohol use, PrEP adherence, retention in care, and condomless sex. Feasibility and acceptability of the intervention will also be examined. Taken together, findings from both phases of this research will not only provide much needed insight into the possible impact of hazardous alcohol use and concurrent conditions on PrEP treatment, but they will also have the potential to guide future initiatives aimed at enhancing PrEP treatment effectiveness.